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VEGF receptor-2 variants are associated with susceptibility to stroke and recurrence.

Abstract：

BACKGROUND AND PURPOSE:Dysregulation of vessel wall formation, growth, and maintenance may confer susceptibility of stroke. METHODS:We tested the hypothesis that variants in 2 genes encoding vascular endothelial growth factor and vascular endothelial growth factor receptor-2 are associated with susceptibility to stroke and its recurrence in a Chinese case-control study comprising 1849 patients with stroke and 1798 control subjects and replicated the investigation in an independent study comprising 327 cases and 327 control subjects. The correlation of variants with carotid artery intima media thickness was examined in 1123 healthy individuals. RESULTS:Compared with their corresponding wild-type genotypes, one coding variant, rs2305948 (Val297Ile), in the vascular endothelial growth factor receptor-2 gene was associated with increased susceptibility to intracerebral hemorrhage (additive model: OR, 2.06; 95% CI, 1.64 to 2.59; P=7.6x10(-10); dominant model: OR, 2.20; 95% CI, 1.70 to 2.84; P=1.5x10(-9)), a promoter variant rs2071559 (-604T>C) in the gene was associated with reduced susceptibility to atherothrombotic stroke (additive model: OR, 0.82; 95% CI, 0.71 to 0.93; P=0.003; dominant model: OR, 0.78; 95% CI, 0.65 to 0.92; P=0.004) and was reversely correlated with carotid artery intima media thickness (P=2.8x10(-5)). Replication in the second study yielded similar results. During a median 4.5 years of follow-up for the first stroke population, 355 recurrent strokes were documented. Subjects carrying 297Ile had a higher risk for stroke recurrence (relative risk, 1.40; 95% CI, 1.12 to 1.75; P=0.003), and those with -604C had a lower risk for recurrence (relative risk, 0.71; 95% CI, 0.58 to 0.89; P=0.002) than their wild-type carriers. CONCLUSIONS:The vascular endothelial growth factor receptor-2 gene variants may serve as novel genetic markers for the risk of stroke and its recurrence.

journal_name

Stroke

journal_title

Stroke

authors

Zhang W,Sun K,Zhen Y,Wang D,Wang Y,Chen J,Xu J,Hu FB,Hui R

doi

10.1161/STROKEAHA.109.554394

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

2720-6

issue

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.109.554394

journal_volume

pub_type

杂志文章,多中心研究

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VEGF receptor-2 variants are associated with susceptibility to stroke and recurrence.